Long-term synaptic changes in two input pathways into the lateral nucleus of the amygdala underlie fear extinction

Plasticity in two input pathways into the lateral nucleus of the amygdala (LA), the medial prefrontal cortex (mPFC) and the sensory thalamus, have been suggested to underlie extinction, suppression of a previously acquired conditioned response (CR) following repeated presentations of the conditioned stimulus (CS). However, little is known about the joint dynamics of the relevant synaptic changes within the LA that accompany fear extinction. Employing a novel training procedure, in which stimulation of the medial geniculate nucleus (MGm) of the thalamus served as the CS, we tested necessary and sufficient conditions for extinction in anesthetized rats. Repeatedly applying the brain-stimulation CS was neither sufficient to produce activation of the mPFC nor behavioral extinction when the animal was under anesthesia. Only when the CS was combined with contingent stimulation of the infralimbic cortex (IL) of the mPFC was the CR markedly reduced, emulating extinction. To elucidate the nature of synaptic alterations linking the extinction procedure with CR suppression, evoked field potentials to IL and MGm stimulations were recorded in the LA. The results showed that paired stimulations of the IL and MGm significantly enhanced the neural response at the IL-LA synapses and reversed conditioning-induced synaptic potentiation at the MGm-LA synapses. Taken together, our results provide strong evidence that dual plasticity within the LA underlies suppression of conditioned fear response following extinction.